DESCRIPTION: (adapted from the application). The, present study has two main goals: (1) to determine the timing of beta- amyloid plaque formation and neuro-degeneration; and (2) to characterize beta-amyloid plaques in the brain of kokanee salmon (Oncorhynchus nerka kennerlyi) during three life-stages: sexually immature (pre-migratory), sexually maturing (migrating and rapidly again), and sexually mature (spawning, senescent). Accumulation of the protein fragment beta-amyloid as plaques in the brain is a central focus of studies of mammalian neuropathology. In fact, Alzheimer's disease, Down's syndrome, and normal aging are characterized pathologically by the presence of beta-amyloid plaques and associated neurofibrillary tangles (NFT). Semelparous Pacific salmon, which die after their first and only reproductive event, exhibit somatic signs of senescence throughout migration and spawning that are similar to age-related changes in humans and other mammals. However, the brain of salmon has not been thoroughly examined. Preliminary studies indicate immunopositive beta-amyloid plaque deposits in spawning (n=5) but not sexually immature (n=4) salmon. In the present study the investigator will utilize general histology (silver stain, congo red, and cresyl violet) and immunohistochemistry (beta-amyloid, apoE, apoptosis and tau) for a more stringent study of neurodegeneration and plaque formation during the three salmon life stages (6-8 month period). Western blot analyses will establish that beta-amyloid (1-40) exists in salmon brain and will be used to verify absence of cross-reactivity of mammalian antibodies with other salmon proteins. The salmon's predictable life history make it an ideal model system to investigate the biochemical process of plaque formation in a wild organism and to study the role of stress and reproductive hormones in brain aging. This model system could be valuable: To this investigator s knowledge, no other model for beta-amyloid research offers these advantages. The long-term goal is to establish beta-amyloid plaques as a biomarker for brain aging in salmon. Plaque formation could be used to study the "aging clock" in salmon.